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Lookup NU author(s): Professor Mark BakerORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s).Fatigue is one of the most debilitating symptoms for people with multiple sclerosis (PwMS). By consolidating a diverse and conflicting evidence-base, this systematic review and meta-analysis aimed to gain new insights into the neurobiology of MS fatigue. MEDLINE, ProQuest, CINAHL, Web of Science databases and grey literature were searched using Medical Subject Headings. Eligible studies compared neuroimaging and neurophysiological data between people experiencing high (MS-HF) versus low (MS-LF) levels of perceived MS fatigue, as defined by validated fatigue questionnaire cut-points. Data were available from 66 studies, with 46 used for meta-analyses. Neuroimaging studies revealed lower volumetric measures in MS-HF versus MS-LF for whole brain (22.74 ml; 95% CI: -37.72 to -7.76 ml; p = 0.003), grey matter (18.81 ml; 95% CI: 29.60 to 8.03 ml; p < 0.001), putamen (0.40 ml; 95% CI: 0.69 to 0.10 ml; p = 0.008) and acumbens (0.09 ml; 95% CI: 0.15 to 0.03 ml; p = 0.003) and a higher volume of T1-weighted hypointense lesions (1.10 ml; 95% CI: 0.47 to 1.73 ml; p < 0.001). Neurophysiological data showed reduced lower-limb maximum voluntary force production (19.23 N; 95% CI: 35.93 to 2.53 N; p = 0.02) and an attenuation of upper-limb (5.77%; 95% CI:8.61 to 2.93%; p < 0.0001) and lower-limb (2.16%; 95% CI:4.24 to 0.07%; p = 0.04) skeletal muscle voluntary activation, accompanied by more pronounced upper-limb fatigability (5.61%; 95% CI: -9.57 to -1.65%; p = 0.006) in MS-HF versus MS-LF. Results suggest that MS fatigue is characterised by greater cortico-subcortical grey matter atrophy and neural lesions, accompanied by neurophysiological decrements, which include reduced strength and voluntary activation. Prospero registration Prospero registration number: CRD42016017934
Author(s): Ellison PM, Goodall S, Kennedy N, Dawes H, Clark A, Pomeroy V, Duddy M, Baker MR, Saxton JM
Publication type: Review
Publication status: Published
Journal: Neuropsychology Review
Year: 2022
Volume: 32
Pages: 506-519
Print publication date: 01/09/2022
Online publication date: 07/05/2021
Acceptance date: 14/04/2021
ISSN (print): 1040-7308
ISSN (electronic): 1573-6660
Publisher: Springer
URL: https://doi.org/10.1007/s11065-021-09508-1
DOI: 10.1007/s11065-021-09508-1
Data Access Statement: Data from the included primary studies is available in the supplementary tables and figures.
